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Diabetes mellitus and other underlying conditions in patients with coronavirus disease 2019 associated rhino-orbito-cerebral mucormycosis: a systematic review and meta-analysis

Part of: JLO Coronavirus Collection

Published online by Cambridge University Press:  06 May 2022

H Zobairy ,
M M Salem ,
M Ghajarzadeh ,
O Mirmosayyeb  and
M Mirsalehi Open the ORCID record for M Mirsalehi [Opens in a new window]
H Zobairy
Affiliation:
Department of Otolaryngology, Kurdistan University of Medical Sciences, Sanandaj, Iran
M M Salem
Affiliation:
Department of Otorhinolaryngology and Head & Neck Surgery, Amir-Alam Hospital, Tehran University of Medical Sciences, Tehran, Iran
M Ghajarzadeh
Affiliation:
Universal Council of Epidemiology (UCE), Universal Scientific Education and Research Network (USERN), Tehran University of Medical Sciences, Tehran, Iran
O Mirmosayyeb
Affiliation:
Universal Council of Epidemiology (UCE), Universal Scientific Education and Research Network (USERN), Tehran University of Medical Sciences, Tehran, Iran
M Mirsalehi*
Affiliation:
ENT and Head & Neck Research Centre, The five Senses Health Institute, School of Medicine, Iran University of medical sciences, Tehran, Iran
*
Author for correspondence: Dr M Mirsalehi, ENT and Head & Neck Research Centre, Hazrat Rasoul Hospital, Sattarkhan Street, Tehran 1445613131, Iran E-mail: mirsalehi.m@iums.ac.ir Fax: +98 216 652 5329
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Abstract

Objective

This study aimed to compute the pooled prevalence of diabetes mellitus and other underlying conditions in patients with coronavirus disease 2019 associated rhino-orbito-cerebral mucormycosis.

Method

A systematic literature review was performed in PubMed, Scopus, Web of Science, Embase and Google Scholar. The cross-sectional studies that reported the frequency of diabetes mellitus in patients with coronavirus disease 2019 associated rhino-orbito-cerebral mucormycosis were included.

Results

Eighteen eligible studies with a total number of 3718 patients were included in the current study. The pooled prevalence of diabetes in patients with coronavirus disease 2019 associated rhino-orbito-cerebral mucormycosis was 89 per cent and with new-onset diabetes was 32 per cent. The pooled prevalence of steroid use was high (79 per cent) too. The all-cause mortality rate was 24 per cent.

Conclusion

Diabetes mellitus was the most frequent underlying condition in patients with coronavirus disease 2019 associated rhino-orbito-cerebral mucormycosis. The second most frequent underlying condition was steroid use during coronavirus disease 2019 infection. The appropriate control of hyperglycaemia and rational prescription of steroids during the treatment of coronavirus disease 2019 associated rhino-orbito-cerebral mucormycosis is recommended.

Keywords

COVID-19Diabetes MellitusPrevalenceMucormycosis

Information

Type
Review Article
Information
The Journal of Laryngology & Otology , Volume 136 , Issue 9 , September 2022 , pp. 788 - 798
Copyright
Copyright © The Author(s), 2022. Published by Cambridge University Press on behalf of J.L.O. (1984) LIMITED

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Footnotes

Dr M Mirsalehi takes responsibility for the integrity of the content of the paper

References

Roden, MM, Zaoutis, TE, Buchanan, WL, Knudsen, TA, Sarkisova, TA, Schaufele, RL et al. Epidemiology and outcome of zygomycosis: a review of 929 reported cases. Clin Infect Dis 2005;41:634–53CrossRefGoogle ScholarPubMed
Chander, J, Kaur, M, Singla, N, Punia, RPS, Singhal, SK, Attri, AK et al. Mucormycosis: battle with the deadly enemy over a five-year period in India. J Fungi 2018;4:46CrossRefGoogle Scholar
Hussain, S, Riad, A, Singh, A, Klugarová, J, Antony, B, Banna, H et al. Global prevalence of Covid-19-associated mucormycosis (CAM): living systematic review and meta-analysis. J Fungi 2021;7:985CrossRefGoogle ScholarPubMed
Liu, J, Li, S, Liu, J, Liang, B, Wang, X, Wang, H et al. Longitudinal characteristics of lymphocyte responses and cytokine profiles in the peripheral blood of SARS-CoV-2 infected patients. EBioMedicine 2020;55:102763CrossRefGoogle ScholarPubMed
Ackermann, M, Verleden, SE, Kuehnel, M, Haverich, A, Welte, T, Laenger, F et al. Pulmonary vascular endothelialitis, thrombosis, and angiogenesis in Covid-19. N Engl J Med 2020;383:120–8CrossRefGoogle ScholarPubMed
Rawson, TM, Moore, LSP, Zhu, N, Ranganathan, N, Skolimowska, K, Gilchrist, M et al. Bacterial and fungal coinfection in individuals with coronavirus: a rapid review to support Covid-19 antimicrobial prescribing. Clin Infect Dis 2020;71:2459–68Google ScholarPubMed
Petrikkos, G, Skiada, A, Lortholary, O, Roilides, E, Walsh, TJ, Kontoyiannis, DP. Epidemiology and clinical manifestations of mucormycosis. Clin Infect Dis 2012;54:23–34CrossRefGoogle ScholarPubMed
Gebremariam, T, Lin, L, Liu, M, Kontoyiannis, DP, French, S, Edwards, JE et al. Bicarbonate correction of ketoacidosis alters host-pathogen interactions and alleviates mucormycosis. J Clin Invest 2016;126:2280–94CrossRefGoogle ScholarPubMed
Wu, C-T, Lidsky, PV, Xiao, Y, Lee, IT, Cheng, R, Nakayama, T et al. SARS-CoV-2 infects human pancreatic β cells and elicits β cell impairment. Cell Metab 2021;33:1565–76.e5CrossRefGoogle ScholarPubMed
Moorthy, A, Gaikwad, R, Krishna, S, Hegde, R, Tripathi, KK, Kale, PG et al. SARS-CoV-2, uncontrolled diabetes and corticosteroids-an unholy trinity in invasive fungal infections of the maxillofacial region? A retrospective, multi-centric analysis. J Maxillofac Oral Surg 2021;20:418–25CrossRefGoogle ScholarPubMed
Jeong, W, Keighley, C, Wolfe, R, Lee, WL, Slavin, MA, Kong, DCM et al. The epidemiology and clinical manifestations of mucormycosis: a systematic review and meta-analysis of case reports. Clin Microbiol Infect 2019;25:26–34CrossRefGoogle ScholarPubMed
Nithyanandam, S, Jacob, MS, Battu, RR, Thomas, RK, Correa, MA, D'Souza, O. Rhino-orbito-cerebral mucormycosis. A retrospective analysis of clinical features and treatment outcomes. Indian J Ophthalmol 2003;51:231–6Google ScholarPubMed
Stang, A. Critical evaluation of the Newcastle-Ottawa scale for the assessment of the quality of nonrandomized studies in meta-analyses. Eur J Epidemiol 2010;25:603–5CrossRefGoogle ScholarPubMed
Higgins, JPT. Measuring inconsistency in meta-analyses. BMJ 2003;327:557–60CrossRefGoogle ScholarPubMed
Arora, R, Goel, R, Khanam, S, Kumar, S, Shah, S, Singh, S et al. Rhino-orbito-cerebral-mucormycosis during the Covid-19 second wave in 2021 - a preliminary report from a single hospital. Clin Ophthalmol 2021;15:3505–14CrossRefGoogle ScholarPubMed
Bhanuprasad, K, Manesh, A, Devasagayam, E, Varghese, L, Cherian, LM, Kurien, R et al. Risk factors associated with the mucormycosis epidemic during the Covid-19 pandemic. Int J Infect Dis 2021;111:267–70CrossRefGoogle ScholarPubMed
Dave, TV, Gopinathan Nair, A, Hegde, R, Vithalani, N, Desai, S, Adulkar, N et al. Clinical presentations, management and outcomes of rhino-orbital-cerebral mucormycosis (rocm) following Covid-19: a multi-centric study. Ophthalmic Plast Reconstr Surg 2021;37:488–95CrossRefGoogle ScholarPubMed
Desai, EJ, Pandya, A, Upadhya, I, Patel, T, Banerjee, S, Jain, V. Epidemiology, clinical features and management of rhino orbital mucormycosis in post COVID 19 patients. Indian J Otolaryngol Head Neck Surg 2021;74:103–7CrossRefGoogle ScholarPubMed
Desai, SM, Gujarathi-Saraf, A, Agarwal, EA. Imaging findings using a combined MRI/CT protocol to identify the “entire iceberg” in post-Covid-19 mucormycosis presenting clinically as only “the tip.” Clin Radiol 2021;76:784.e27–784.e33CrossRefGoogle ScholarPubMed
Dubey, S, Mukherjee, D, Sarkar, P, Mukhopadhyay, P, Barman, D, Bandopadhyay, M et al. Covid-19 associated rhino-orbital-cerebral mucormycosis: an observational study from Eastern India, with special emphasis on neurological spectrum. Diabetes Metab Syndr Clin Res Rev 2021;15:102267CrossRefGoogle ScholarPubMed
Gupta, DP, Gupta, S, Shah, CK, Sreevidya, SR. Clinical study of surge of mucormycosis in Covid-19 pandemic: a tertiary care center study. Indian J Otolaryngol Head Neck Surg. 10.1007/s12070-021-02784-6. Epub 2021 Aug 4Google Scholar
Joshi, AR, Muthe, MM, Patankar, SH, Athawale, A, Achhapalia, Y. CT and MRI findings of invasive mucormycosis in the setting of Covid-19: experience from a single center in India. AJR Am J Roentgenol 2021;217:1431–2CrossRefGoogle ScholarPubMed
Kumari, A, Rao, NP, Patnaik, U, Malik, V, Tevatia, MS, Thakur, S et al. Management outcomes of mucormycosis in Covid-19 patients: a preliminary report from a tertiary care hospital. Med J Armed Forces India 2021;77:S289–95CrossRefGoogle ScholarPubMed
Mangal, R, Gehlot, PS, Bang, A, Kaushal, A, Kolare, R. Covid-19 associated rhino-orbito-cerebral mucormycosis: clinical profile and imaging spectrum. J Clin Diagnostic Res 2021;15:TC01–6Google Scholar
Mishra, Y, Prashar, M, Sharma, D, Akash Kumar, VP, Tilak, TVSVGK. Diabetes, Covid 19 and mucormycosis: Clinical spectrum and outcome in a tertiary care medical center in Western India. Diabetes Metab Syndr Clin Res Rev 2021;15:102196CrossRefGoogle Scholar
Pakdel, F, Ahmadikia, K, Salehi, M, Tabari, A, Jafari, R, Mehrparvar, G et al. Mucormycosis in patients with Covid-19: a cross-sectional descriptive multicentre study from Iran. Mycoses 2021;64:1238–52CrossRefGoogle ScholarPubMed
Paras, P, Purvi, P, Brijeshkumar, S, Arunima, B, Drasti, P, Maitri, B. Expanding the spectrum of fatal necrotizing fungal infections presented as sinonasal and rhino orbital mucormycosis and aspergillosis in post coronavirus disease. Eur J Mol Clin Med 2021;8:101–10Google Scholar
Ramaswami, A, Sahu, AK, Kumar, A, Suresh, S, Nair, A, Gupta, D et al. Covid-19-associated mucormycosis presenting to the emergency department—an observational study of 70 patients. QJM An Int J Med 2021;114:464–70CrossRefGoogle Scholar
Selarka, L, Sharma, S, Saini, D, Sharma, S, Batra, A, Waghmare, VT et al. Mucormycosis and Covid-19: an epidemic within a pandemic in India. Mycoses 2021;64:1253–60CrossRefGoogle ScholarPubMed
Sen, M, Honavar, SG, Bansal, R, Sengupta, S, Rao, R, Kim, U et al. Epidemiology, clinical profile, management, and outcome of Covid-19-associated rhino-orbital-cerebral mucormycosis in 2826 patients in India - Collaborative OPAI-IJO Study on Mucormycosis in Covid-19 (COSMIC), Report 1. Indian J Ophthalmol 2021;69:1670–92Google Scholar
Sharma, S, Grover, M, Bhargava, S, Samdani, S, Kataria, T. Post-coronavirus disease mucormycosis: a deadly addition to the pandemic spectrum. J Laryngol 2021;135:442–7CrossRefGoogle Scholar
Thayyil, J, Divakaran, A, Anikkady, N. Covid-19 associated mucormycosis during the second wave of pandemic in South India. Int J Res Med Sci 2021;9:1CrossRefGoogle Scholar
Pai, V, Sansi, R, Kharche, R, Bandili, SC, Pai, B. Rhino-orbito-cerebral mucormycosis: pictorial review. Insights Imaging 2021;12:167CrossRefGoogle ScholarPubMed
Chouhan, M, Solanki, B, Shakrawal, N. Rhino-orbital-cerebral mucormycosis: fungal epidemic in a viral pandemic. J Laryngol Otol 2021;135:981–6CrossRefGoogle Scholar
Pradhan, P, Shaikh, Z, Mishra, A, Preetam, C, Parida, PK, Sarkar, S et al. Predisposing factors of rhino-orbital-cerebral mucormycosis in patients with Covid 19 infection. Indian J Otolaryngol Head Neck Surg 2021;10.1007/s12070-021-02875-4. Epub 2021 Sep 25CrossRefGoogle ScholarPubMed
Patel, A, Agarwal, R, Rudramurthy, SM, Shevkani, M, Xess, I, Sharma, R et al. Multicenter epidemiologic study of coronavirus disease – associated methods. Emerg Infect Dis 2021;27: 2349–59CrossRefGoogle Scholar
Singh, AK, Singh, R, Joshi, SR, Misra, A. Mucormycosis in Covid-19: a systematic review of cases reported worldwide and in India. Diabetes Metab Syndr Clin Res Rev 2021;15:102146CrossRefGoogle ScholarPubMed
Muthu, V, Rudramurthy, SM, Chakrabarti, A, Agarwal, R. Epidemiology and pathophysiology of Covid-19-associated mucormycosis: India versus the rest of the world. Mycopathologia 2021;186:739–54CrossRefGoogle ScholarPubMed
Hussain, S, Baxi, H, Riad, A, Klugarová, J, Pokorná, A, Slezáková, S et al. Covid-19-associated mucormycosis (CAM): an updated evidence mapping. Int J Environ Res Public Health 2021;18:10340CrossRefGoogle ScholarPubMed
Alba-Loureiro, TC, Munhoz, CD, Martins, JO, Cerchiaro, GA, Scavone, C, Curi, R et al. Neutrophil function and metabolism in individuals with diabetes mellitus. Brazilian J Med Biol Res 2007;40:1037–44CrossRefGoogle ScholarPubMed
Morales-Franco, B, Nava-Villalba, M, Medina-Guerrero, EO, Sánchez-Nuño, YA, Davila-Villa, P, Anaya-Ambriz, EJ et al. Host-pathogen molecular factors contribute to the pathogenesis of rhizopus spp. in diabetes mellitus. Curr Trop Med Reports. 2021;8:6–17CrossRefGoogle Scholar
Ghuman, H, Voelz, K. Innate and adaptive immunity to mucorales. J Fungi 2017;3:48CrossRefGoogle ScholarPubMed
Narayanan, S, Chua, J V, Baddley, JW. Coronavirus disease 2019–associated mucormycosis: risk factors and mechanisms of disease. Clin Infect Dis 2021;74:1279–83CrossRefGoogle Scholar
Reed, C, Bryant, R, Ibrahim, AS, Edwards, JJ, Filler, SG, Goldberg, R et al. Combination polyene-caspofungin treatment of rhino-orbital-cerebral mucormycosis. Clin Infect Dis 2008;47:364–71CrossRefGoogle ScholarPubMed
Vaughan, C, Bartolo, A, Vallabh, N, Leong, SC. A meta-analysis of survival factors in rhino-orbital-cerebral mucormycosis—has anything changed in the past 20 years? Clin Otolaryngol 2018;43:1454–64CrossRefGoogle ScholarPubMed
Corzo-León, DE, Chora-Hernández, LD, Rodríguez-Zulueta, AP, Walsh, TJ. Diabetes mellitus as the major risk factor for mucormycosis in Mexico: epidemiology, diagnosis, and outcomes of reported cases. Med Mycol 2018;56:29–43CrossRefGoogle ScholarPubMed
Shrestha, DB, Budhathoki, P, Raut, S, Adhikari, S, Ghimire, P, Thapaliya, S et al. New-onset diabetes in Covid-19 and clinical outcomes: a systematic review and meta-analysis. World J Virol 2021;10:275–87CrossRefGoogle ScholarPubMed
Goddanti, N, Reddy, YM, Kumar, MK, Rajesh, M, Reddy, LS. Role of Covid 19 inflammatory markers in rhino-orbito-cerebral mucormycosis: a case study in predisposed patients at a designated nodal centre. Indian J Otolaryngol Head Neck Surg 2021;10.1007/s12070-021-02970-6. Epub 2021 Nov 13CrossRefGoogle Scholar
Gupta, S, Ahuja, P. Risk factors for procurence of mucormycosis and its manifestations post Covid-19: a single arm retrospective unicentric clinical study. Indian J Otolaryngol Head Neck Surg 2021; 34567997. Epub 2021 Sep 18CrossRefGoogle ScholarPubMed
Riad, A, Shabaan, AA, Issa, J, Ibrahim, S, Amer, H, Mansy, Y et al. Covid-19-associated mucormycosis (CAM): case-series and global analysis of mortality risk factors. J Fungi 2021;7:837CrossRefGoogle ScholarPubMed
Dilek, A, Ozaras, R, Ozkaya, S, Sunbul, M, Sen, EI, Leblebicioglu, H. Covid-19-associated mucormycosis: case report and systematic review. Travel Med Infect Dis 2021;44:102148CrossRefGoogle ScholarPubMed
Zirpe, K, Pote, P, Deshmukh, A, Gurav, SK, Tiwari, AM, Suryawanshi, P. A retrospective analysis of risk factors of Covid-19 associated mucormycosis and mortality predictors: a single-center study. Cureus 2021;13:e18718Google ScholarPubMed
Pal, R, Singh, B, Bhadada, SK, Banerjee, M, Bhogal, RS, Hage, N et al. Covid-19-associated mucormycosis: an updated systematic review of literature. Mycoses 2021;64:1452–9CrossRefGoogle ScholarPubMed
Pippal, SK, Kumar, D, Ukawat, L. Management challenge of rhino-orbito-cerebral mucormycosis in Covid 19 era: a prospective observational study. Indian J Otolaryngol Head Neck Surg 2021;34722223. Epub 2021 Oct 23CrossRefGoogle ScholarPubMed
Prakash, H, Ghosh, AK, Rudramurthy, SM, Singh, P, Xess, I, Savio, J et al. A prospective multicenter study on mucormycosis in India: epidemiology, diagnosis, and treatment. Med Mycol 2019;57:395–402CrossRefGoogle Scholar
Tian, W, Jiang, W, Yao, J, Nicholson, CJ, Li, RH, Sigurslid, HH et al. Predictors of mortality in hospitalized Covid-19 patients: a systematic review and meta-analysis. J Med Virol 2020;92:1875–83CrossRefGoogle ScholarPubMed
Ssentongo, P, Ssentongo, AE, Heilbrunn, ES, Ba, DM, Chinchilli, VM. Association of cardiovascular disease and 10 other pre-existing comorbidities with Covid-19 mortality: a systematic review and meta-analysis. PLoS One 2020;15:1–16CrossRefGoogle ScholarPubMed
Recovery collaborative group. Dexamethasone in hospitalized patients with Covid-19. N Engl J Med 2021;384:693–704CrossRefGoogle Scholar
Lionakis, MS, Kontoyiannis, DP. Glucocorticoids and invasive fungal infections. Lancet 2003;362:1828–38CrossRefGoogle ScholarPubMed
Vare, A, Yellambkar, S, Farheen, A, Nandedkar, V, Bhombe, S, Shah, R. Incidence, cumulative mortality and factors affecting the outcome of Covid-19-associated mucormycosis from Western India. Indian J Ophthalmol 2021;69:3678CrossRefGoogle ScholarPubMed
Lanternier, F, Dannaoui, E, Morizot, G, Elie, C, Garcia-Hermoso, D, Huerre, M et al. A global analysis of mucormycosis in France: the retrozygo study (2005–2007). Clin Infect Dis 2012;54:35–43CrossRefGoogle Scholar
Skiada, A, Pavleas, I, Drogari-Apiranthitou, M. Epidemiology and diagnosis of mucormycosis: an update. J Fungi 2020;6:1–20CrossRefGoogle ScholarPubMed
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